Helicobacter pylori diversity and gastro-duodenal disease in Western Africa
Helicobacter pylori (Hp) is causally linked with gastric pre-malignant lesions, gastric cancer (GCA) and peptic ulcer disease (PUD). In Africa, PUD is prevalent while GCA has reportedly low incidence. Less is known about pre-malignant lesions. Hp genes cagA and vacA are established virulence factors and have been associated with increased gastroduodenal disease (GDD) risk. Further, diversity in the Carboxyl-terminus of cagA can influence GCA risk. Virulence studies have evolved from candidate-based to more robust genome wide association studies (GWAS). Here, a clinical and histopathological assessment of GDD in West Africa was performed, as well as an evaluation of associated Hp genetic variation.
In 136 dyspeptic patients from Ghana, pre-malignant lesions had low prevalence, 14.7%, most of which were located distally. vacA and cagA Hp strains were identified by PCR in 69.2% and 74.8% of 159 dyspeptic Ghanaian patients respectively; cagA-(internal duplication region) being more prevalent than cagA-(hydrophilic region). Duodenal ulcer was associated with cagA-(hydrophilic region) and vacAs1m1.
Multi-locus sequence typing (MLST) of seven housekeeping genes have previously identified multiple distinct H. pylori populations or lineages such as hpAfrica1 and hpEurope. An agnostic analysis of Hp virulence employed a GWAS using 193 controls from the European-African admixed population of Cape Verde (CV) and 101 cases from reference databases. African controls and cases clustered within hpAfrica1, while European controls and cases clustered within hpEurope. Genes significant for GCA or PUD were established virulence factors cagPAI, vacA and babA2. Prominent among these were lipopolysaccharide and peptidoglycan biosynthesis proteins. Phylogenetic analyses showed a cluster of closely related CV lineages that diverged from European cases. This CV_outgroup was notable for absence of major virulence genes.
Although several novel and established variants have been linked to GDD, population structure in bacteria can lead to false positives in linkage dysequilibrium (LD) with genuine risk variants. Hence, validation studies are required to assist in risk stratification of infected individuals for further management. Ultimately, GDD risk is multi-factorial. Therefore, studies ought to evaluate host, bacterial and environmental factors in an integrated design.
Supervisor(s)Sandra Beleza; Christopher Bayliss
Date of award2020-12-18
Author affiliationDepartment of Genetics and Genome Biology
Awarding institutionUniversity of Leicester